A photo illustration of Dr. Kang Zhang, chief of eye genetics at the University of California San Diego, with parts of a warning letter and an inspection report from the FDA about his research. (UCSD, inewsource)

In a new development, inewsourceobtained an inspection report from the U.S. Food and Drug Administration that detailed more problems with one of Zhang’s studies. The report, compiled in 2016, described one incident in which Zhang poked a hole in a study participant’s eye with a needle, causing a cataract that had to be fixed with surgery.

The person wasn’t supposed to be enrolled in the study, according to the report, and the injury allegedly occurred because Zhang was in a hurry to take a trip to China.

When people volunteer to be human research subjects, they accept potential health risks in order to contribute to a growing bank of scientific and medical knowledge.

Their medical history, blood, organs or DNA are mined to improve the diagnosis and treatment of diseases, or to develop new technologies to help people live longer, healthier lives.

The researchers are expected to follow ethical guidelines meant to protect their patients.

In a statement emailed Tuesday to inewsource, UCSD said, “The FDA report raises a number of concerning issues, all of which the university takes very seriously. Dr. Zhang is currently on leave. UC San Diego is reviewing Dr. Zhang’s activities and cannot comment further at this time.”

Zhang was suspended from overseeing human research studies in April 2017 but was allowed to continue to apply for federal grants, publish in medical journals and train the next generation of scientists at the university.

inewsource’s reporting on Zhang described how his repeated human research violations over many years highlight ways in which local, state and federal institutions can fail to protect study participants.

Spencer Hey, a bioethicist at Harvard Medical School, reviewed the FDA inspection records and told inewsource, “This is bad for Zhang’s lab, but also bad for UCSD, since it shows that they may lack sufficient checks and oversight to ensure that research conducted at their institution (or under their institutional banner) is in compliance and has appropriate protections for participants.”

Inspections, audits and violations

Zhang’s drug study began in 2011 and sought to reverse the effects of a common eye disease called macular degeneration by injecting people in the eye with a drug once a month.

A study participant – who didn’t fit the enrollment criteria for the drug trial – complained to UCSD shortly after the tests began, stating that Zhang was negligent because he “was in a hurry to leave for China,” which resulted in the doctor “making a hole in the anterior chamber of the left eye, which created a cataract that had to be corrected in a subsequent surgical procedure.”

Photos of the back of the eye showing early (left) and advanced age-related macular degeneration. (National Eye Institute, National Institutes of Health)

“It’s a very rare complication,” said Dr. Peter Campochiaro, an ophthalmology professor at Johns Hopkins Medicine.

“It’s not commonly seen because it’s not that difficult to get the injection in the right place,” said Campochiaro, who also directs the university’s Retinal Cell and Molecular Laboratory.

Genentech, the drug manufacturer, told inewsource it doesn’t comment on third-party investigations such as Zhang’s, but that serious problems related to the injection procedure have occurred in less than 0.1% of injections.

Zhang later said the participant signed off on the risks associated with the research.

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According to the FDA report, UCSD initiated at least three reviews into Zhang’s projects from 2012 to 2014, none of which are publicly available online. At one point, the university suspended enrollment for eight months in his studies.

During the suspension, Zhang enrolled three people and injected them with the drug. That study ended in 2015 because Zhang wasn’t communicating with UCSD.

The next year, the FDA inspection found that Zhang:

Lacked a monitoring plan or procedure to ensure patient safety and oversight.

Had no data monitoring or quality assurance unit.

Failed to administer the drug 10 times to four subjects, despite being required to do so per the study guidelines.

Was missing records about what happened to 25 units of the study drug.

Enrolled people who were not eligible for the study because their eye disease hadn’t progressed enough.

Kept no records about whether serious harmful events had occurred at his other study sites in Bakersfield, Santa Barbara or San Antonio, Texas – nor had he ever visited those sites, because he “assumed” they were following procedures.

The federal inspector noted that Zhang told her “it was a bad time to conduct the inspection since it is the summer and this inspection is interfering with his vacation plans to China.”

The FDA warning letter that followed described some of these violations and said Zhang failed to provide the agency with a plan to keep his subjects safe moving forward. The letter made no mention of a harmful incident.

UCSD published the results of another internal audit of Zhang’s work a month later. It found more violations in the doctor’s other research studies: Zhang and his team tested participants for HIV and AIDS without their permission; gave people incorrect and outdated consent forms to sign; lost documents; and failed to perform required screenings and procedures.

The audit didn’t mention any subjects harmed during the studies.

Hey, from Harvard, told inewsource he found that strange and ethically problematic.

“If results from these studies (or honestly, any study from this lab) were ever published, we should be highly skeptical about the safety data or any safety-related claims,” he said.

Despite repeated attempts, inewsource has been unable to speak with Zhang.

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About Brad Racino:

Brad Racino is a senior investigative reporter and assistant director at inewsource. To contact him with tips, suggestions or corrections, please email bradracino [at] inewsource [dot] org. You can contact him securely on Signal (845-553-4170).